Apremilast refers to (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione and has the following structure:

Apremilast is a small molecule inhibitor of phosphodiesterase (PDE4). Apremilast inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. Apremilast also has anti-inflammatory activity. In 2014, Apremilast was approved by the United States Food and Drug administration for the treatment of active psoriatic arthritis and moderate to severe plaque psoriasis. It is available under the trade name of OTEZLA® as an inhibitor of phosphodieasterase 4 (PDE4) and OTEZLA® tablets are supplied in 10, 20, and 30 mg strengths for oral administration. Apremilast is also being evaluated for its efficacy in treating other chronic inflammatory diseases such as ankylosing spondylitis, Behcet's disease and rheumatoid arthritis.
U.S. Pat. No. 6,020,358 describes racemic 2-[1-(3-ethoxy-4-methoxy phenyl)-2-(methyl sulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide and process for its preparation. U.S. Pat. No. 7,427,638 describes stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, substantially free of its (−) isomer, or a pharmaceutically acceptable metabolite, salt, solvate or hydrate, thereof and its pharmaceutical composition. WO 2012/097116 and U.S. 2014/0081032 describe processes for the preparation of isoindoline compounds and their isotopologues, including apremilast. U.S. 2013/0217918 describes processes for enantioselective preparation of arylmethanesulfonylethylamines using chiral auxiliaries (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine, which is used for the preparation of apremilast. WO 2009/120167 and U.S. Pat. No. 7,893,101 describe various solid forms comprising apremilast including Forms A, B, C, D, E, F and G. WO 2014/072259 describes an anhydrous form of apremilast. U.S. 2015/0283249 describes an amorphous form of apremilast. All references cited herein, including the apremilast products associated with the above-mentioned trade names, are incorporated herein by reference in their entireties.
The preparation and selection of a solid form of a pharmaceutical compound is complex, given that a change in solid form may affect a variety of physical and chemical properties, which may provide benefits or drawbacks in processing, formulation, stability and bioavailability, among other important pharmaceutical characteristics. The importance of studying polymorphs was underscored by the case of Ritonavir, an HIV protease inhibitor that was formulated as soft gelatin capsules. About two years after the product was launched, the unanticipated precipitation of a new, less soluble polymorph in the formulation necessitated the withdrawal of the product from the market until a more consistent formulation could be developed. The preparation of solid forms is of great importance in the development of a safe, effective, stable and marketable pharmaceutical compound. Therefore, provided herein are six novel forms of apremilast, pharmaceutical compositions comprising the novel forms of apremilast and methods for treating disease using such compositions.